S454 IL-23 p19 Blockade Triples 12-Week Clinical and Mucosal Remission Without Added Adverse Events in Moderate-to-Severe Ulcerative Colitis: A Systematic Review and Meta-Analysis of 4 Randomized Controlled Trials

Introduction: Interleukin 23 (IL-23) is pivotal in chronic gut inflammation, yet the impact of isolating its p19 subunit in ulcerative colitis (UC) has only just emerged. Phase-3 trials of mirikizumab, risankizumab and guselkumab each reported strong induction efficacy, but the unified signal and safety picture were unknown. We present the first pooled analysis of all Randomized controlled trials (RCTs) quantifying the class effect of IL-23 p19 blockade, addressing a critical evidence gap amid an increasingly crowded advanced-therapy landscape. Methods: A systematic search of PubMed, Embase, Scopus, and Cochrane Library identified RCTs comparing IL23 p19 blockade drugs versus placebo in managing UC through May 2025. Data were analyzed using RevMan 4.2.1. Pooled risk ratios (RRs) with 95% confidence intervals (CIs) were calculated using Mantel-Haenszel methods. Random- or fixed-effects models were applied based on heterogeneity (Higgins’ I²). Statistical significance was set at P < 0.05. Risk of bias was assessed using RoB 2.0. Results: Among 3,151 participants in 4 RCTs of IL-23 p19 inhibitors (guselkumab, mirikizumab, risankizumab), 12-week induction therapy nearly tripled clinical remission (25.3% vs 9.1%; RR 2.96, 95% CI 1.92–4.58) and markedly enhanced endoscopic outcomes—improvement (37.4% vs 11.7%; RR 3.18, 2.23–4.53), remission (24.1% vs 9.4%; RR 2.80, 1.70–4.63) and composite mucosal healing (22% vs 7%; RR 3.56, 2.00–6.34). Overall adverse-event frequency remained similar to placebo (44.7% vs 48.3%; RR 0.93, 0.85–1.03), while serious events were numerically lower (2.0% vs 6.5%; RR 0.39, 0.15–1.03), underscoring a favorable benefit–risk profile for IL-23 p19 blockade in moderate-to-severe ulcerative colitis. Conclusion: This meta-analysis shows that IL-23 p19 inhibitors nearly triple 12-week clinical and mucosal remission while matching placebo on overall adverse events and hinting at fewer serious harms. Benefit consistency across 3 molecules, despite moderate heterogeneity, confirms a reproducible class effect and positions IL-23 blockade as a potent alternative to TNF-α or JAK inhibition. Clinically, early mucosal healing predicts durable remission, colectomy avoidance and lower neoplasia risk, making the magnitude of endoscopic benefit highly relevant. Our synthesis therefore delivers timely evidence for guideline updates, informs payer decisions, and equips clinicians to adopt this novel therapeutic class with confidence.